A novel HEXB mutation and its structural effects in juvenile Sandhoff disease.
Mutations in HEXB, encoding the beta-subunit common to hexosaminidases A and B, cause the neurodegenerative condition, Sandhoff disease. A homozygous missense HEXB mutation (p. D459A) was discovered in six patients with a rare juvenile variant: we show that this disrupts a salt bridge between aspartate D459 and arginine 505 at the subunit interface; R505 mutations are reported in late-onset Sandhoff disease. Identification of D459A contributes to diagnosis and molecular understanding of attenuated Sandhoff disease variants.
Wang
S Z
SZ
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Cachón-González
M B
MB
Stein
P E
PE
Lachmann
R H
RH
Corry
P C
PC
Wraith
J E
JE
Cox
T M
TM
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D012497:Sandhoff Disease / Q000235:genetics*; D044465:White People / Q000235:genetics; D054821:beta-Hexosaminidase beta Chain / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
C513386:HEXB protein, human; D054821:beta-Hexosaminidase beta Chain